Clinical parameters and nomograms for predicting lymph node metastasis detected with 68 Ga-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy.

BACKGROUND: Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naïve nonmetastatic prostate cancer (PC) patients. MATERIALS AND METHODS: The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves. RESULTS: A total of 288 lymph node metastases were identified in 121 patients (27.3%) using 68 Ga-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS ≥7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF. CONCLUSION: The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from 68 Ga-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, 68 Ga-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning.

Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment.

BACKGROUND: Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed. MATERIALS AND METHODS: The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS. RESULTS: The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis. CONCLUSIONS: MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.

Stereotactic radiotherapy to oligoprogressive lesions detected with 68Ga-PSMA-PET/CT in castration-resistant prostate cancer patients.

PURPOSE: We assessed the outcomes of stereotactic body radiotherapy (SBRT) to treat oligoprogressive castration-resistant prostate cancer (CRPC) patients with ≤5 lesions using gallium prostate-specific membrane antigen-positron emission tomography (68Ga-PSMA-PET/CT). METHODS: The clinical data of 67 CRPC patients with 133 lesions treated with 68Ga-PSMA-PET/CT-based SBRT were retrospectively analyzed. All of the patients had oligoprogressive disease during androgen-deprivation therapy (ADT). The prognostic factors for overall- (OS) and progression-free survival (PFS) and the predictive factors for switching to next-line systemic treatment (NEST) and NEST-free survival (NEST-FS) were analyzed. RESULTS: With a median follow-up of 17.5 months, the 2-year overall survival (OS) and PFS rates were 86.9% and 34.4%, respectively. The PSA response was observed in 49 patients (73.1%). Progression was observed in 37 patients (55.2%) at a median of 11.0 months following SBRT. A total of 45 patients (67.2%) remained on ADT after SBRT, and 22 patients (32.8%) had a NEST change at a median of 16.4 months after metastasis-directed treatment (MDT). Patients with a NEST change had higher post-SBRT PSA values and fewer PSA nadirs after MDT than their counterparts. In multivariate analysis, higher pre-SBRT PSA values were the only significant predictor for worse OS and NEST-FS, and no significant factor was found for PFS. No serious acute or late toxicities were observed. CONCLUSION: This study demonstrated the feasibility of MDT using SBRT to treat oligoprogressive lesions by 68Ga-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST.

Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using 68Ga-PSMA PET/CT: TROD 09-004 Study.

PURPOSE: To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (68Ga-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients. METHODS: In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by 68Ga-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed. RESULTS: The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed. CONCLUSIONS: We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with 68Ga-PSMA PET/CT.

Gemcitabine based trimodality treatment in patients with muscle invasive bladder cancer: May neutrophil lymphocyte and platelet lymphocyte ratios predict outcomes?

PURPOSE: Cisplatin based chemoradiation has been commonly used as a definitive treatment for muscle-invasive bladder cancer (MIBC). The aim of the current study is to evaluate oncologic results and toxicity profile of bladder-sparing treatment with external beam radiotherapy (EBRT) and gemcitabine chemotherapy (ChT) in patients with MIBC. MATERIALS AND METHODS: Between April 2005 and November 2018 44 patients with nonmetastatic and N0 MIBC were treated with transurethral resection of bladder (TURB), EBRT and concurrent gemcitabine. All patients were staged using thorax-abdomen-pelvic CT and pelvic MRI. EBRT was delivered using 3D conformal technique or intensity modulated radiotherapy. Patients received 50 Gy in 25 to 28 fractions to full bladder followed by a boost dose of 10 Gy in 5 fractions to empty bladder with weekly concurrent gemcitabine of 50 mg/m2. All patients were evaluated for age, gender, smoking status, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) at diagnosis, presence of hydroureteronephrosis (HUN), preoperative tumor size, tumor multifocality, presence of CIS, clinical tumor stage. Acute/late genitourinary (GUS) and gastrointestinal (GIS) toxicity, recurrence status, cancer specific survival (CSS) and overall survival (OS) were evaluated. Statistical analysis was performed using SPSS v21.0. Kaplan-Meier survival estimates were calculated to describe CSS and OS. The effect of different parameters on survival was investigated using the log rank test. RESULTS: Median age of the patients was 72 years (interquartile [IQR]; 66-80). The median tumor size was 30 mm (IQR, 15-59 mm). Thirty-two (77%) patients had T2, 6 (14%) patients had T3, and 4 (9%) patients had T4a disease. Median NLR was 2.6 (IQR, 1.7-3.8) and median PLR was 126.47 (IQR, 77.4-184.8). Median follow-up time was 21 months (range, 6-153 months). At the first TURB performed 6 weeks after CRT, complete response, partial response, stable disease, and progression was detected in 37 (84%), 3 (7%), 1 (2%), and 3 (7%) patients, respectively. One- and 2-year OS, CSS, LRFS, and DMFS rates were 86% and 64%; 88% and 66%; 65% and 44%; 68% and 48%, respectively. In univariate analysis; prognostic factors were age and presence of HUN for OS and DMFS; age, HUN, presence of CIS, NLR, and PLR for DSS; HUN, NLR, and PLR for LRFS, respectively. In multivariate analysis, the independent predictor was the presence of HUN for OS, LRFS, and DMFS; NLR for DSS; PLR for LRFS and age for DMSF. For a subgroup of 17 patients with complete TURB and no CIS and HUN symptoms, 2-year OS, DSS, LRFS, and DMFS rates were 88%, 88%, 72%, and 79%, respectively. The treatment was well-tolerated and all patients completed the planned EBRT and ChT. No acute or late ≥ grade 3 toxicity was observed. Grade II acute GIS toxicity was detected in 3 (7%) patients and grade II acute GUS toxicity was detected in 9 (21%) patients, respectively. Grade II late GUS toxicity was observed in 2 (5%) patients. CONCLUSION: Gemcitabine based trimodality treatment is well-tolerated with similar oncologic outcomes reported in the literature. Older age, presence of CIS and high NLR and PLR values seem to deteriorate DSS.

Factors affecting post-treatment radiation-induced lung disease in patients receiving stereotactic body radiotherapy to lung.

The aim of the study is to investigate factors that may cause radiation-induced lung disease (RILD) in patients undergoing stereotactic body radiotherapy (SBRT) for lung tumors. Medical records of patients treated between May 2018 and June 2019 with SBRT were retrospectively evaluated. All patients should have a diagnosis of either primary non-small cell lung cancer (NSCLC) or less than three metastases to lung from another primary. The median treatment dose was 50 Gy in 4-5 fractions. Tumor response and RILD were evaluated in thoracic computer tomography (CT) using RECIST criteria. 82 patients with 97 lung lesions were treated. The median age was 68 years (IQR = 62-76). With a median follow-up of 7.2 months (3-18 months), three patients had grade 3 radiation pneumonitis (RP). RILD was observed in 52% of cases. Patients who had RILD had a higher risk of symptomatic RP (p = 0.007). In multivariate analyses older age, previous lung radiotherapy history, and median planning treatment volume (PTV) D95 value of ≥ 48 Gy were associated with RILD. Local recurrence (LR) was observed in 5.1% of cases. There was no difference in overall survival and LR with the presence of RILD. Older age, previous lung radiotherapy history, and median PTV D95 value of ≥ 48 Gy seems to be associated with post-SBRT RILD.

Role of 68-Ga-PSMA-PET/CT in pelvic radiotherapy field definitions for lymph node coverage in prostate cancer patients.

PURPOSE: To evaluate the distribution of metastatic lymph nodes (LN) detected on 68Ga-PSMA-positron emission tomography/computed tomography (PET/CT) in treatment-naïve prostate cancer (PC) patients and to analyze the LN coverage rates of the pelvic fields defined in the GETUG trial and RTOG guidelines and a pelvic field extending superiorly from the L4/L5 interspace. MATERIALS AND METHODS: 68Ga-PSMA-PET/CT images obtained at diagnosis of 138 PC patients were retrospectively analyzed. The number and locations of 68Ga-PSMA-positive LNs were co-registered with one single-planning CT. The numbers, locations, and sizes of LNs located outside the three pelvic volumes were investigated for the entire cohort and for patients with LN metastasis in the pelvic area only. RESULTS: A total of 441 PSMA-PET-positive LN metastases were identified. The most frequent metastatic LNs were internal iliac LNs (25.2%). Para-aortic and presacral LNs outside the three pelvic fields were present in 20 (14.5%) and 22 patients (15.9%), respectively. The LN coverage rates according to the GETUG trial, the RTOG guidelines, and the pelvic field extending superiorly from L4/L5 were 44.2%, 52.2%, and 71, respectively, in the entire cohort and 51.7%, 61 and 83.1%, respectively, in patients with only pelvic LN metastasis. The number of metastatic LNs was a predictive factor for LNs located outside the three pelvic fields. CONCLUSIONS: Extending the cranial margin of the pelvic field from L5/S1 to L4/L5 increases the accuracy of pelvic field irradiation in approximately 20% of patients, highlighting the importance of proximal common iliac irradiation, particularly in patients with multiple LN metastasis.

Treatment outcomes of metastasis-directed treatment using 68Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

PURPOSE: The aim of this study was to evaluate the outcomes of 68Ga prostate-specific membrane antigen (68Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC). METHODS: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with 68Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation. RESULTS: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2­year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2­year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT. CONCLUSION: 68Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.

Stereotactic body radiotherapy in patients with early-stage non-small cell lung cancer: Does beam-on time matter?

PURPOSE: Stereotactic body radiotherapy (SBRT) is an effective treatment option for patients with early-stage non-small cell lung cancer (NSCLC). In this study, we evaluated the treatment results using two different SBRT techniques and the effect of beam-on time (BOT) on treatment outcomes. METHODS: Between July 2007 and January 2018, 142 patients underwent SBRT for primary NSCLC. We have delivered SBRT using either respiratory tracking system (RTS) or internal-target-volume (ITV)-based motion management techniques. The effect of age, tumor size, pretreatment tumor SUVmax value, presence of tissue diagnosis, histopathological subtype, operability status, tumor location, motion management technique, BED10 value, BOT on overall survival (OS), loco-regional control (LRC), event-free survival (EFS) and primary tumor control (PTC) were evaluated. RESULTS: Median age of the patients was 70 years (range, 39-91 years). Most of the patients were inoperable (90%) at the time of SBRT. Median BED10 value was 112.5 Gy. With a median follow-up of 25 months, PTC was achieved in 91.5% of the patients. Two-year estimated OS, LRC, PTC and EFS rates were 68, 63, 63 and 53%, respectively. For the entire group, OS was associated with BOT (P = 0.027), and EFS was associated with BOT (P = 0.027) and tumor size (P = 0.015). For RTS group, OS was associated with age (P = 0.016), EFS with BOT (P = 0.05) and tumor size (P = 0.024), LRC with BOT (P = 0.008) and PTC with BOT (P = 0.028). The treatment was well tolerated in general. CONCLUSION: SBRT is an effective and safe treatment with high OS, LRC, EFS and PTC rates in patients with primary NSCLC. Protracted BOT might deteriorate SBRT outcomes.

Determination of inflection points of CyberKnife dose profiles within acceptability criteria of deviations in measurements.

AIM: The aim of this study was to determine the Inflection Points (IPs) of flattening filter free (FFF) CyberKnife dose profiles for cone-based streotactic radiotherapy. In addition, dosimetric field sizes were determined. BACKGROUND: The increased need for treatment in the early stages of cancer necessitated the treatment of smaller tumors. However, efforts in that direction required the modeling accuracy of the beam. Removal of the flattening filter (FF) from the path of x-ray beam has provided the solution to those efforts, but required a different normalization approach for the beam to ensure the delivery of the dose accurately. As a solution, researchers proposed a normalization factor based on IPs. MATERIALS AND METHODS: Measurements using microDiamond (PTW 60019), Diode SRS (PTW 60018) and Monte Carlo (MC) calculations of dose profiles were completed at SAD 80 cm and 5 cm depth for 15-60 mm cones. Performance analysis of detectors with respect to MC calculation was carried out. Gamma evaluation method was used to determine achievable acceptability criteria for FFF CyberKnife beams. RESULTS: Acceptability within (3%-0.5 mm) was found to be anachievable criterion for all dose profile measurements of the cone beams used in this study. To determine the IP, the first and second derivatives of the dose profile were determined via the cubic spline interpolation technique. CONCLUSION: Derivatives of the interpolated profiles showed that locations of IPs and 50% isodose points coincide.

Adjuvant vaginal cuff brachytherapy: dosimetric comparison of conventional versus 3-dimensional planning in endometrial cancer.

PURPOSE: To evaluate dosimetric differences between point-based 2-dimensional (2D) vaginal brachytherapy (VBT) treatment planning technique and volume-based 3-dimensional (3D) VBT method for endometrial cancer (EC). MATERIAL AND METHODS: Ten patients with uterine-confined EC treated with VBT were included in this study. All patients received 27.5 Gy in 5 fractions. Three different treatment plans were performed for each patient: plan A for dose prescribed to the entire vaginal wall thickness delineated via computed tomography guidance, plan B for dose prescribed to the vaginal mucosa/cylinder surface, and plan C for dose prescribed to 5 mm beyond the vaginal mucosa/cylinder surface. Dose-volume histograms (DVH) of treatment volumes and organs at risk (OARs) were evaluated and compared. RESULTS: DVH analysis of target volume doses (D100, D95, and D90) showed a significant difference between plan A and plan B (p = 0.005), and plan B was found lower. D100 for plan C was significantly higher than plan A (p = 0.009), but for D95 and D90, no statistically significant difference was found (p = 0.028 and p = 0.028, respectively). In terms of OARs doses, including vagina, rectum, bladder, and sigmoid, D2cm3 doses were significantly higher in plan A than plan B (p = 0.009, p = 0.009, p = 0.005, and p = 0.005, respectively). All these doses were also significantly lower than in plan C (p = 0.005, p = 0.012, and p = 0.013, respectively), except for sigmoid (p = 0.155). CONCLUSIONS: In this dosimetric analysis, we have shown that the volume-based 3D VBT technique provides the ability to balance the target dose against the sparing of OARs. Therefore, in the new modern 3D treatment era, instead of normalization of the dose to standard reference points, customized 3D volume-based VBT planning should be recommended.

Prognostic significance of castrate testosterone levels for patients with intermediate and high risk prostate cancer.

BACKGROUND: Testosterone level of < 50 ng/dL has been used to define castrate level after surgery or after androgen deprivation treatment (ADT) in metastatic prostate cancer (PC). AIM: To evaluate the effect of two different castrate testosterone levels, < 50 and < 20 ng/dL, on biochemical relapse free survival (BRFS) in patients with non-metastatic intermediate and high risk PC receiving definitive radiotherapy (RT) and ADT. METHODS: Between April 1998 and February 2011; 173 patients with intermediate and high risk disease were treated. Radiotherapy was delivered by either three-dimensional-conformal technique to a total dose of 73.4 Gy at the ICRU reference point or intensity modulated radiotherapy technique to a total dose of 76 Gy. All the patients received 3 mo of neoadjuvant ADT followed by RT and additional 6 mo of ADT. ASTRO Phoenix definition was used to define biochemical relapse. RESULTS: Median follow up duration was 125 months. Ninety-six patients (56%) had castrate testosterone level < 20 ng/dL and 139 patients (80%) had castrate testosterone level < 50 ng/dL. Both values are valid at predicting BRFS. However, patients with testosterone < 20 ng/dL have significantly better BRFS compared to other groups (P = 0.003). When we compare two values, it was found that using 20 ng/dL is better than 50 ng/dL in predicting the BRFS (AUC = 0.63 vs 0.58, respectively). CONCLUSION: Castrate testosterone level of less than 20 ng/dL is associated with better BRFS and is better in predicting the BRFS. Further studies using current standard of care of high dose IMRT and longer ADT duration might support these findings.

Integration of 68Ga-PSMA-PET/CT in Radiotherapy Planning for Prostate Cancer Patients.

To assess the role of Gallium-labeled-prostate-specific membrane antigen PET/CT (Ga-PSMA-PET/CT) in risk group definition and radiotherapy planning in the initially planned definitive radiotherapy (RT) for prostate cancer patients. METHODS: The clinical data of 191 prostate cancer patients treated with definitive intensity-modulated RT were retrospectively analyzed. All patients were initially staged with thoracoabdominal CT and bone scintigraphy, and the second staging was performed using Ga-PSMA-PET/CT. Both stages were evaluated for the decision making of RT and any change in RT target volumes. RESULTS: After staging with Ga-PSMA-PET/CT, 26 patients (13.6%) had risk group changes, 16 patients (8.4%) had an increase in risk group, and 10 patients (5.2%) had a decrease in risk group. Down-staging occurred in 22 patients (11.5%), and upstaging was observed in 30 patients (15.7%). A total of 26 patients (13.6%) had nodal stage changes. After the Ga-PSMA-PET/CT scans, the number of metastatic patient increased to 17 (8.9%), with 4 of them moving from oligo- to polymetastatic disease. An additional irradiation of pelvic lymphatics and metastatic site was performed in 13 patients (6.8%) and 6 patients (3.2%), respectively. The RT was aborted in 4 patients (2.1%) because of parenchymal or distant site metastasis observed in the Ga-PSMA-PET/CT. CONCLUSIONS: We found that Ga-PSMA-PET/CT causes considerable migration in stage, risk group, and RT field arrangements, especially in high-risk patients regardless of the GS and baseline prostate-specific antigen values alone. Ga-PSMA-PET/CT seems to have a great influence on RT decision making in prostate cancer patients.

Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

PURPOSE: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era. METHODS: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT. RESULTS: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5­year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10. CONCLUSIONS: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.

Evaluation of NanoDot Optically Stimulated Luminescence Dosimeter for Cone-shaped Small-field Dosimetry of Cyberknife Stereotactic Radiosurgery Unit: A Monte Carlo Simulation and Dosimetric Verification Study.

AIM: The aim of this study was to investigate the adequacy of nanoDot optically stimulated luminescence (OSL) dosimeter for small field dosimetry before its in vivo applications in CyberKnife SRS unit. MATERIALS AND METHODS: A PTW 60018 SRS Diode, 60019 microDiamond, and Gafchromic EBT3 films were used along with a nanoDot carbon-doped aluminum oxide OSL dosimeter to collect and compare beam data. In addition, the EGSnrc/BEAMnrc code was employed to simulate 6-MV photon beams of CyberKnife SRS system. RESULTS: All detectors showed good consistency with each other in output factor measurements for cone sizes of 15 mm or more. The differences were maintained within 3% for these cones. However, OSL output factors showed higher discrepancies compared to those of other detectors for smaller cones wherein the difference reached nearly 40% for cone size of 5 mm. Depending on the performance of OSL dosimeter in terms of output factors, percentage depth doses (PDDs) were only measured for cones equal to or larger than 15 mm. The differences in PDD measurements were within 5% for depths in the range of 5-200 mm. CONCLUSION: Its low reliable readings for cones smaller than 15 mm should be considered before its in vivo applications of Cyberknife system.

68Ga-labelled PSMA ligand HBED-CC PET/CT imaging in patients with recurrent prostate cancer.

BACKGROUND: 68Ga-PSMA Positron Emission Tomography/Computerized Tomography (PET/CT) has shown promising results for the detection of recurrent prostate cancer (RPCa). However, the diagnostic value of this method is yet to be validated. The aim of this study was to determine the influence of clinical and biochemical variables on the detection rate of 68Ga-PSMA PET/CT in patients with RPCa. METHODS: This is a prospective study of 121 patients who underwent 68Ga-PSMA-PET/CT and conventional imaging (CI) for RPCa. Detection rates were analyzed and correlated with various clinical and biochemical variables such as Gleason score GS), androgen deprivation therapy (ADT), trigger PSA (tPSA), PSA doubling-time (PSAdt) and PSA velocity (PSAv). RESULTS: 68Ga-PSMA-PET/CT showed at least one focus of pathological 68Ga-PSMA uptake in 92/121 (76%) of patients. Nodal metastases (in 47% of patients) were the most common site of recurrent disease followed by bones (36%) and prostate (32%). Out of 121 patients, 57 (47%) had only positive findings on PSMA scan verified by biopsy or follow-up. The majority of these lesion were located in the lymph nodes (31/57, 54,5%), which were below the detection limit of CT. Univariate analysis showed higher detection rate of PET/CT with increasing tPSA, PSAv and short PSAdt. Best cutoff for tPSA, PSAv and PSAdt was 0.5 ng/ml, 2.25 ng/ml/year and 8.65 months, respectively. The detection rate of PSMA-PET/CT was higher in patients with high grade tumors (GS > 7, 23.7% vs 76.3%) and in patients who were on ADT during of PSMA scan (76.3% vs 96%). In multiple logistic regression analysis, PSAdt and concurrent ADT were identified as predictors of positive 68Ga-PSMA-PET/CT. CONCLUSION: 68Ga-PSMA-PET/CT is useful for re-staging patients with RPCa and has improved performance compared with CI for disease detection. Detection rates are improved in patients on ADT and with short PSAdt.

Reirradiation of Pediatric Tumors Using Hypofractionated Stereotactic Radiotherapy.

BACKGROUND: This study aimed to evaluate the efficacy and safety of hypofractionated stereotactic radiotherapy for reirradiation of recurrent pediatric tumors. METHODS AND MATERIALS: The study included 23 pediatric patients who were reirradiated using hypofractionated stereotactic radiotherapy in the radiation oncology department between January 2008 and November 2013. In total, 33 tumors were treated-27 (82%) cranial and 6 (18%) extracranial. Hypofractionated stereotactic radiotherapy was administered due to recurrent disease in 31 (94%) tumors and residual disease in 2 (6%) tumors. The median total dose was 25 Gy (range: 15-40 Gy), and the median follow-up was 20 months (range: 2-68 months). RESULTS: The 1-year and 2-year local control rates in the entire study population were 42% and 31%, respectively. The median local control time was 11 months (range: 0-54 months) following hypofractionated stereotactic radiotherapy. The patients with tumor response after hypofractionated stereotactic radiotherapy had significantly longer local control than the patients with post-hypofractionated stereotactic radiotherapy tumor progression (21 vs 3 months, P < .001). Tumor volume <1.58 cm3 was correlated (not significantly) with better local control (23 vs 7 months, P = .064). CONCLUSION: Reirradiation of pediatric tumors using hypofractionated stereotactic radiotherapy is a safe and effective therapeutic approach. This treatment modality should be considered as a treatment option in selected pediatric patients.

PREVENTION OF RADIATION-INDUCED RETINOPATHY WITH AMIFOSTINE IN WISTAR ALBINO RATS.

PURPOSE: To evaluate the radioprotective efficacy of amifostine on irradiated mature rat retina. METHODS: A total of 108 Wistar albino rats were categorized into 3 groups, namely, apoptosis (n = 48), acute effects (n = 40), and late changes in retinal cell layers (n = 20). Each group was further subcategorized into 4 arms: control, amifostine (A), radiotherapy + placebo (RT), and RT + A arms, respectively. Intraperitoneal amifostine (260 mg/kg) was administrated to A and RT + A arms 30 minutes before irradiation. Control and A groups were sham-irradiated, whereas a single dose of 20 Gy whole-cranium irradiation was delivered to RT and RT + A arms. Apoptosis was assessed in 8, 12, and 18 hours after irradiation. Electron microscope was used 2 weeks after irradiation for evaluation and scoring of early morphologic changes in retina. Late effects were assessed and scored accordingly by using both the electron and the light microscope on Week 10. RESULTS: At acute phase, although no notable change was seen in 8 hours, significant increase in apoptosis was detected in 12 hours in RT arm (P = 0.029). Comparative analyses between the groups in 3 different time points displayed a higher apoptotic rate in RT group than the RT + A group (P = 0.008). Similarly, comparisons between groups for late effects on the basis of electron microscopic findings revealed lower scores in the RT + A than the RT arm (P < 0.001). CONCLUSION: This study suggested a potential radioprotective role for amifostine on mature rat retina by reducing radiation-induced apoptosis in retinal cells. These results form a basis for such preclinical investigations and call for future clinical studies.

Hypofractionated stereotactic reirradiation for recurrent glioblastoma.

Treatment choices for recurrent glioblastoma patients are sparse and the results are not satisfactory. In this retrospective analysis, we evaluated the results of re-irradiation of locally recurrent glioblastoma patients with an image-guided, fractionated, frameless stereotactic radiotherapy (SRT) technique. We treated 37 patients with the diagnosis of recurrent glioblastoma from September 2009 to December 2011. SRT was performed in a median five fractions (range, 1-5 fractions) with CyberKnife(®) (Accuray Incorporated, Sunnyvale, CA, USA). The dose given ranged from 14 to 32 Gy (median, 30 Gy). The median volume of the GTV was 24 cc (range, 2-81 cc). Median follow-up was 9.3 months. Five patients had regression in their lesions, 14 had stable disease, progression was observed in eight patients, and seven patients had pseudoprogression. The median survival following SRT was 10.6 months (range, 1.1-20 months) and overall survival following initial treatment was 35.5 months. The time to progression following SRT was 7.9 months in median. Patients with pseudoprogression had significantly longer survival after the first magnetic resonance imaging (MRI) compared to those with regression, stable or progressive disease (p = 0.012). The median survival after SRT for patients with pseudoprogression was 20 months. Patients who had GTV <24 cc had significantly longer survival following SRT compared to those with lesions ≥24 cc (p = 0.015). Patients who had chemotherapy after SRT had a median survival of 16.8 months. This was 9.7 months for patients who were not prescribed any chemotherapy (p = 0.062).